Centinel™ Intelligent Virus Defense

MVM Resistance through Genetic Engineering

Contamination in the manufacturing process can be a rare but catastrophic event costing a company millions per contamination in clean-up costs alone. This does not include any loss of revenue due to missed product sales or the impact to the patient population due to loss of drug supply. Even with the use of animal origin free and animal component free systems, there have been recorded contaminations of CHO cells by Minute Virus of Mice (MVM) also called Mouse Minute Virus (MMV).

MilliporeSigma's unwavering commitment to be on the leading edge of virus resistance for industry advancement and betterment has led us to a completely new approach to viral safety. Our Centinel™ technology leverages a powerful combination of MilliporeSigma’s tailored biologic solutions and advanced gene editing technology to ensure manufacturing processes are both secure and sustainable. Centinel™ delivers true organizational value by reducing the risk of contamination, and in doing so, supports patient safety. It goes beyond viral insurance - it is smart science and an essential advancement in viral risk reduction.

As part of the Centinel™ brand promise to enable the development of better biologics and safer manufacturing processes, we have identified a gene target (SLC35A1) that upon elimination of expression by gene editing, results in a CHO cell line that is resistant to infection by MVM. In addition, protein titer is not affected by this modification.

In conjunction with our colleagues at BioReliance, we are able to provide a complete offering of ZFN gene editing reagents, gene editing services and MVM resistance assays to help strengthen your risk reduction efforts.

Zinc Finger Nuclease (ZFN) Targeting SLC35A1

ZFNs are a class of engineered DNA-binding proteins that facilitate targeted editing of the genome by creating double-strand breaks in DNA at user-specified locations. ZFN gene editing reagents have been designed to target CHO SLC35A1 for the purpose of generating an MVM resistant CHO cell line.

Gene Editing Services

In addition to purchasing the ZFN reagent, clients can utilize the CHOZN team’s expertise in gene editing services to generate an MVM resistant cell line. Cell line engineering projects are divided into phases so that invoicing only occurs after completion of a phase. Technical communication between your R&D team and ours allows the project to move smoothly through the phases with mutual agreement between teams to progress with the project.

Stage

Description

Estimated Time (in Weeks)

1

Program Initiation and Technology Transfer

1

2

1ZFN Preparation

4

3

1Cell Line Equivalency Studies

6

3

ZFN Transfection and Activity Confirmation

2

4

Single Cell Cloning and Characterization

8–12

5

2MVM Resistance Assays

TBD

6

2Mycoplasma and Sterility Testing and Clone Delivery

TBD

1These stages will be performed in parallel.
2Time and cost to be provided by a current quote from BioReliance.

Validation of MVM Resistance

MVM resistance assays have been developed by BioReliance and are now offered as a free-standing service or in conjunction with a cell line engineering project. Contact BioReliance directly or email CHOZN@sial.com.